tbuckley/cabot-search huggingface dataset:
Patterns of relapse after immunotherapy in patients with high-risk neuroblastoma.
Authors: Scott Moerdler, Arlene Naranjo, Sheena Tenney, Rochelle Bagatell, Alice L. Yu, Wendy B. London
Journal: Journal of Clinical Oncology (2022)

10043 Background: While the addition of anti-GD2 immunotherapy led to improvement in outcomes in patients on the Children’s Oncology Group (COG) ANBL0032 study, relapse remains a concern. Prior studies demonstrated the prognostic importance of time to first relapse, however, the effect of immunotherapy on timing and patterns of relapse in neuroblastoma (NBL) have yet to be evaluated. The purpose of this exploratory analysis was to describe the impact of immunotherapy on patterns of relapse in patients with high-risk NBL, including a descriptive comparison of sites of relapse based on post-consolidation treatment received [dinutuximab with cytokines and isotretinoin (DIN) vs isotretinoin alone (ISO)]. Methods: A retrospective, descriptive analysis of patients on ANBL0032 was performed, including patients randomized to DIN or ISO and those non-randomly assigned to DIN after ISO arm closure. Pt characteristics including age, stage, MYCN amplification status, tumor grade, mitosis-karyorrhexis index (MKI) and ploidy were summarized descriptively and relapse sites were tabulated. For DIN patients who subsequently relapsed, overall survival (OS) was calculated starting from the time of first relapse after enrollment on ANBL0032 (“post-relapse OS”). Kaplan-Meier OS curves were generated based on site of relapse. Results: The analytic cohort included 1,431 (DIN = 1,327; ISO = 104) patients. Among DIN patients, 492 relapsed, many in &gt; 1 site. In the randomized cohort (n = 248), 122 relapsed (DIN = 68/144; ISO = 54/104). The frequencies (DIN; ISO) by site of relapse in the randomized cohort were: bone (53%; 54%), CNS (16%; 11%), lymph node (13%; 17%), abdominal (10%; 17%), paraspinal (6%; 2%), liver (3%; 4%), other soft tissue (22%; 7%). A higher proportion of ISO patients had marrow relapse (29.4% DIN; 48.2% ISO); however, the proportion of DIN patients with lung relapses appeared higher (9% vs 2%). Among all relapsed patients, the proportion with bone relapse did not appear to differ between treatment groups, regardless of MYCN status. Among patients with MYCN amplified disease, the proportion with marrow relapse did not appear to differ based on treatment [21/149 (14.1%) DIN; 3/20 (15.0%) ISO]; however, among patients with MYCN non-amplified disease, the proportion with marrow relapse appeared higher in the ISO group [16/23; 69.6%] vs the DIN group [52/193 (26.9%)]. Conclusions: In this exploratory analysis of patients on COG ANBL0032, the pattern for site of relapse appears to differ between patients treated with DIN vs ISO. While immunotherapy remains the treatment of choice in this population, the findings from this retrospective exploratory analysis warrant further investigation to decrease the risk for post-immunotherapy relapse. Clinical trial information: NCT00026312.
Analysis of peripheral neuropathy (PN) using clinician- and patient-reported outcomes (ClinRO and PRO) in the POLARIX study.
Authors: Marek Trneny, Laura Fogliatto, Faithlore Patrice Gardner, Ian W. Flinn, Jean-Francois Larouche, Corinne Haioun, Miguel Angel Canales Albendea, Hideki Goto, Roman Hajek, Gilles A. Salles, Jiaheng Qiu, Avrita Campinha-Bacote, Mark Yan, Rucha Kothari, Gabriel Man, Deniz Sahin, Jamie Hirata, Calvin Lee, Herve Tilly, Christopher Flowers
Journal: Journal of Clinical Oncology (2022)

7561 Background: PN is an identified risk of anti-microtubule agents, including polatuzumab vedotin and vincristine. POLARIX (NCT03274492), a Phase III randomized, double-blind, placebo-controlled study comparing Pola-R-CHP with R-CHOP, demonstrated improved progression-free survival (PFS) with Pola-R-CHP (Tilly et al. NEJM 2022). Here, we evaluate the impact of Pola-R-CHP vs R-CHOP on PN using ClinRO and PRO data. Methods: Patients with previously untreated diffuse large B-cell lymphoma (DLBCL) received Pola-R-CHP or R-CHOP. ClinRO data were based on PN grading according to the NCI CTCAE v4.0. PRO data were generated from assessment of patient-reported PN symptoms at baseline and Day 1 of each cycle using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group – Neurotoxicity (FACT-GOG/NTX) subscale, ranging from 0–44, with higher scores representing lower levels of PN (minimal clinically important difference: 1.38–3.68 [Cheng et al. Health Qual Life Outcomes 2020]). Results: At baseline, ClinRO and PRO symptom scores showed low PN burden (Table). Overall incidence of PN was comparable between treatment arms (Pola-R-CHP: 52.9%; R-CHOP: 53.9%); most events were grade 1, and incidence of grade 2 (Pola-R-CHP: 12.2%; R-CHOP: 15.5%) and grade 3 (Pola-R-CHP: 1.6%; R-CHOP: 1.1%) events were comparable between treatment arms. FACT-GOG/NTX survey completion was high in both arms (96% at baseline; &gt;80% at other timepoints). When evaluated by cycle, ClinRO and PRO demonstrated that more patients experienced earlier onset PN with R-CHOP than with Pola-R-CHP (Table), with ̃10% more R-CHOP- than Pola-R-CHP-treated patients having clinician-reported PN in Cycle (C) 2–5, and a ̃+1-point difference (i.e. fewer symptoms) in PRO symptom scores in C3–6 with Pola-R-CHP vs R-CHOP; by C8+, and during follow up, rates and symptoms of PN were similar. PN symptoms resulted in fewer dose reductions (3.9% vs 8.2%) and drug discontinuations (0.7% vs 2.1%) with Pola-R-CHP vs R-CHOP. Duration of PN was similar for both treatments. Conclusions: In the POLARIX study, Pola-R-CHP did not result in different rates or severity of PN vs R-CHOP. According to ClinRO and PRO data, PN occurred later following initial exposure to Pola-R-CHP than to R-CHOP, and there were fewer dose modifications with Pola-R-CHP than with R-CHOP. Overall, the risk of PN was manageable. Clinical trial information: NCT03274492. [Table: see text]
Pathogenesis and treatment of multiple myeloma
Authors: Peipei Yang, Ying Qu, Mengyao Wang, Bingyang Chu, Wen Chen, Yuhuan Zheng, Ting Niu, Zhiyong Qian
Journal: MedComm (2022)

Multiple myeloma (MM) is the second-ranking malignancy in hematological tumors. The pathogenesis of MM is complex with high heterogeneity, and the development of the disease is a multistep process. Chromosomal translocations, aneuploidy, genetic mutations, and epigenetic aberrations are essential in disease initiation and progression. The correlation between MM cells and the bone marrow microenvironment is associated with the survival, progression, migration, and drug resistance of MM cells. In recent decades, there has been a significant change in the paradigm for the management of MM. With the development of proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, chimeric antigen receptor T-cell therapies, and novel agents, the survival of MM patients has been significantly improved. In addition, nanotechnology acts as both a nanocarrier and a treatment tool for MM. The properties and responsive conditions of nanomedicine can be tailored to reach different goals. Nanomedicine with a precise targeting property has offered great potential for drug delivery and assisted in tumor immunotherapy. In this review, we summarize the pathogenesis and current treatment options of MM, then overview recent advances in nanomedicine-based systems, aiming to provide more insights into the treatment of MM.
Real-world treatment outcomes from nationwide Onco-colon Turkey registry in RAS wi̇ld-type patients treated with biologics second-line mCRC.
Authors: Mahmut Emre Yildirim, Mustafa Karaca, Mehmet Artac, Irfan Cicin, Caglayan Geredeli, Ahmet Alacacioglu, Eda Tanrikulu Simsek, Ahmet Bilici, Hakan Harputluoglu, Melike Ozcelik, Oktay Bozkurt, Sinemis Yuksel, Deniz Tural, Abdullah Sakin, Timucin Cil, Basak Bala Oven, Faysal Dane, Duygu Cevik, Mahmut Gumus, Abdurrahman Isikdogan
Journal: Journal of Clinical Oncology (2022)

e15562 Background: Varieties of systemic treatments in second-line treatment for metastatic colorectal cancer (mCRC) patients have showed an improvement on survival. In this context, most of mCRC patients are likely to progress and to change from first line to second line treatment when they develop resistance to first-line treatment options. Therefore, we aimed to investigate second-line treatment selection in patients with RAS-wild type mCRC. Methods: Medical records from 28 centers were collected for patients diagnosed with RAS wild-type and were included into the study. Histopathological, molecular and clinical characteristics of the patients were recorded. The treatment duration, response rate, progression-free survival and safety results were determined. Patients were compared according to the second-line biological treatments as anti-EGFR group (Group A and B; panitumumab and cetuximab) and anti-VEGF group (group C; bevacizumab or aflibercept). Results: A total of 1064 patients with documented RAS wild-type status were evaluated. Fifty-six percent of all first line patients were treated with regimen including biologics received second line treatment. Median age was 60 years. 34,7 percent of the patients were female. Nineteen percent of the patients had a right-sided colon tumor. 16,3 %, 22,5% and 61,2 % of all second-line patients were treated with regimen including panitumumab, cetuximab and anti-VEGF, respectively. Patients received median 5 (1-21) cycles of treatment. Also, responded patients received median 4 (1-23) cycles of treatment as maintenance treatment with biologics plus fluoropyrimidine. Overall response rate was 28,5 % for all patients. Disease control rate also was 70,6 %. The median OS was 15,7, 14,3, and 14,7 months in A, B and C group respectively (p = 0.764). The median PFS of the patients in second-line setting that received panitumumab, cetuximab and bevacizumab/ aflibercept were 7,8, 6,6 and 7,4 months respectively (p = 0.848). There was not found as independent prognostic factors in multivariate analysis. Conclusions: According to the results of our real-life data study, there is no significant difference in efficacy between the combinations of biological agent and chemotherapy used in the second-line treatments. Therefore, the results of the first-line treatment become important and the use of the most effective agent at this setting also increases survival.
Colored perfusion areas-based 3D virtual models: The Rainbow Kidney as a new tool to optimize the clamping strategy during robot-assisted partial nephrectomy
Authors: D. Amparore, F. Piramide, A. Pecoraro, E. Checcucci, S. De Cillis, A. Piana, P. Verri, S. Granato, M. Sica, M. Burgio, B. Carbonaro, M. Manfredi, C. Fiori, F. Porpiglia
Journal: European Urology (2022)
Treatment outcomes for men with stage 2 non-seminoma undergoing primary RetroPeritoneal Lymph Node Dissection (RPLND): A systematic review
Authors: A. Neuenschwander, C. Lonati, A. Papachristofilou, R. Cathomas, C. Rothermund, A.J. Templeton, A. Gulamhusein, S. Fischer, S. Gillessen, T. Hermanns, A. Mattei, A. Lorch, C.D. Fankhauser
Journal: European Urology (2022)
Large-scale genomic analysis of renal cell carcinoma using 1,532 Japanese patients and 5,996 controls
Authors: Y. Sekine, Y. Iwasaki, T. Aoi, E. Mikiko, M. Hirata, Y. Kamatani, K. Matsuda, S. Kokichi, T. Yoshida, Y. Murakami, T. Fukui, S. Akamatsu, O. Ogawa, H. Nakagawa, K. Numakura, S. Narita, Y. Momozawa, T. Habuchi
Journal: European Urology (2022)
Global multi-center phase I trial of the intraperitoneal infusion of anti-EpCAM x anti-CD3 bispecific antibody catumaxomab for advanced gastric carcinoma with peritoneal metastasis.
Authors: Changsong QI, Shikai Wu, In-Ho Kim, Shirong Cai, Jufeng Wang, Seung Tae Kim, Jaw-Yuan Wang, Li-Yuan Bai, Cheng-Yao Lin, Zhezhao Liang, Jian Xin Wei, Lin Shen
Journal: Journal of Clinical Oncology (2022)

e16102 Background: Advanced gastric cancer (GC) patients (pts) have high incidence of peritoneal metastasis (PM), resulting in ascites, cachexia and poor life quality. EpCAM is highly expressed on GC but no on peritoneum. Catumaxomab intraperitoneal infusion (i.p.) was previously demonstrated to eradicate EpCAM+ cancers and control the malignant ascites in Europe (Heiss. Int. J. Cancer.2010). We present initial safety, pharmacokinetics (PK), and efficacy from the multi-center phase I trial of Catumaxomab on GC pts with PM in Asian population (NCT04222114). Methods: GC pts who had progressed on at least two prior standard systemic therapies with peritoneal metastasis were enrolled. Pts received Catumaxomab i.p. of 10 μg, 20 μg, 50 μg and 150 μg on days 1, 4, 8 and 11, respectively in the 1 st cycle. From the 2 nd cycle, Pts received Catumaxomab i.p. of 20 μg, 50 μg, 150 μg on days 1, 4 and 8, respectively. The cycle was 42 days in Cohort A, and 28 days in Cohort B. Catumaxomab PK were evaluated, tumor measurements and quantification of ascites by five-point method (Oriuchi, JJCO,2005) were performed Q6W. The primary endpoint was overall survival (OS); secondary endpoints were response rate of ascites, progression-free interval of peritoneal metastatic lesions and puncture-free survival (PuFS); Data cut-off date was Jan 29,2022. Results: 17 pts from 14 sites (median age: 52.5 yr, ECOG PS: 0 [n=2], 1 [n=14], 2[n=1], Cohort A:9, Cohort B:8) were treated. There were no dose-limiting toxicities (DLTs). The most common treatment-emergent adverse event (TEAE) was pyrexia (76.5%) and abdominal pain (58.8%). Grade ≥3 treatment related adverse events (TRAE) of abdominal pain (23.5%), bilirubin conjugated increased (23.5%), lymphocyte count decreased (17.6%), ALT increased (11.8%), and AST increased (11.8%) were reported. No treatment related death or neurotoxicity occurred in the study. Median overall survival was 102 days (95%CI: 38-166), with 10 (58.8%) deaths observed. For ascites, CR+PR was observed in 4 cases (33%), no PD case was reported. No therapeutic ascites drainage was recorded after cycle 1. Median PuFS was 116 days (95%CI: 28-157). Median progression-free interval of peritoneal metastatic lesions was 102 days (95%CI: 38-166). PK: Catumaxomab concentrations in plasma increased in a dose-dependent manner and were similar to Caucasian population in Europe. Conclusions: This clinical study indicated that multiple cycles of Catumaxomab i.p. were safe and well tolerated in Asian population. PK profile was similar. Early efficacy signals were promising, especially in pts with ascites, which will be further investigated in phase 3 study. Clinical trial information: NCT04222114.
Integration of molecular cancer classification and NGS to identify patients with metastatic cancer eligible for BRAF inhibitors.
Authors: Harry E. Fuentes Bayne, Li Ma, Jenna Wong, Kai Treuner, Thorvardur Ragnar Halfdanarson
Journal: Journal of Clinical Oncology (2022)

e15118 Background: Melanoma, non-small cell lung cancer (NSCLC), colorectal adenocarcinoma and thyroid tumors frequently harbor BRAF mutations and are tumor types eligible for treatment with FDA-approved BRAF inhibitors. Although there are many ongoing clinical trials with BRAF inhibitors in various advanced tumor types, currently eligibility requires both tumor type identification and BRAF mutation confirmation. The 92-gene assay (CancerTYPE ID) is a gene expression-based classifier of 50 tumor types and subtypes for metastatic patients with diagnostic ambiguity. Multimodal biomarker testing, including NGS, IHC and FISH, enables identification of actionable biomarkers to guide targeted therapy selection. Here, a database of metastatic cases integrating tumor type with biomarker analysis was used to identify patients eligible for BRAF inhibitor treatment. Methods: MOSAIC (Molecular Synergy to Advance Individualized Cancer Care) is an IRB-approved, de-identified database of diagnostically ambiguous cases submitted for CancerTYPE ID testing with tumor type-guided multimodal biomarker testing (Neogenomics). In this study, metastatic cancers of various tumor types with BRAF mutations were identified. Results: CancerTYPE ID determined 27 different tumor types in 2929 (92.5%) of 3168 cases. BRAF mutations were identified in 87 cases across 18 tumor types and subtypes. Out of the 87 cases, 22 (25.3%) had BRAF mutations in a tumor type eligible for FDA-approved BRAF inhibitor treatment, including melanoma, NSCLC, colorectal adenocarcinoma and thyroid cancer. Another 26 (29.9%) BRAF-mutated cases were detected in a tumor type with ongoing BRAF inhibitor clinical trials, including lymphoma, pancreaticobiliary and ovarian cancer (Table). Conclusions: This analysis identified patients with metastatic cancer with actionable BRAF mutations eligible for FDA-approved therapy, and patients who may be eligible for investigational BRAF inhibitors based on tumor type and mutation status. Notably, cancer type identification is critical given that FDA-approved BRAF inhibitor treatment regimens vary based on the tumor-specific indication. These findings support the clinical utility of molecular tumor type classification by CancerTYPE ID combined with biomarker profiling to identify additional treatment options for patients with metastatic cancer.[Table: see text]
Mammary adipocytes protect triple-negative breast cancer cells from ferroptosis
Authors: Yizhao Xie, Biyun Wang, Yannan Zhao, Zhonghua Tao, Ye Wang, Guangliang Chen, Xichun Hu
Journal: Journal of Hematology & Oncology (2022)

Ferroptosis, a novel non-apoptotic form of cell death, can induce tumor cell death and treatment resistance. Lipid metabolism is closely related to ferroptosis; however, the effect of mammary adipocytes on breast cancer ferroptosis remains to be elucidated. Here, we established the co-culture system of adipocyte-breast cancer cells and revealed the protection of triple-negative breast cancer from ferroptosis by adipocytes. Then, we performed the lipidomics analysis comparing lipid metabolites of co-cultured and normal-cultured cells. Mechanistically, oleic acid secreted from adipocytes inhibited lipid peroxidation and ferroptosis of triple-negative breast cancer cells in the presence of ACSL3. Taken together, mammary adipocytes can protect breast cancer cells from ferroptosis through oleic acid in the presence of ACSL3. These findings could provide new ideas and targets for tumor treatment.
Real-world effectiveness of immune checkpoint inhibitors alone or in combination with chemotherapy in metastatic non–small cell lung cancer.
Authors: Lingzhi Hong, Waree Rinsurongkawong, Maliazurina B Saad, Pingjun Chen, Muhammad Aminu, Amy R. Spelman, Marcelo Vailati Negrao, Tina Cascone, Steven H. Lin, Percy Lee, Boris Sepesi, Jeff Lewis, Don Lynn Gibbons, Ara A. Vaporciyan, J. Jack Lee, Xiuning Le, Jia Wu, John Heymach, Jianjun Zhang, Natalie I Vokes
Journal: Journal of Clinical Oncology (2022)

9055 Background: The benefit of combination immune checkpoint inhibitor (ICI) with chemotherapy over ICI monotherapy in non-small cell lung cancer (NSCLC) remains underexplored. Methods: This retrospective cohort included patients with metastatic NSCLC from a single-institution database treated with ICI monotherapy or with chemotherapy between 1/2014-2/2020. Clinical progression-free survival (PFS) and overall survival (OS) were the primary outcomes. Propensity score adjustment for clinical and sociodemographic characteristics was used for analysis of first-line treatment outcomes. Results: A total of 1,139 patients (54% male; median age, 64.9) were included. Adenocarcinoma histology, smoking history, higher PD-L1 expression, and lower metastatic stage associated with improved PFS. However, PD-L1 expression and smoking associated with PFS only in adenocarcinoma (LUAD); squamous (LUSC) patients had shorter PFS independent of PD-L1 and smoking history (PD-L1 &gt; 50% vs 1-49%: LUAD P &lt; 0.001; LUSC P = 0.69; Former vs never smoker: LUAD P = 0.008; LUSC P = 0.89). In first-line patients (n = 680), treatment with ICI plus chemotherapy (ICI-chemo) associated with higher progression-free rates at 3 and 6 months compared with ICI-monotherapy (ICI-chemo vs ICI-mono: 3-month PFS, 85.2% vs 68.8%, P = 0.001; 6-month PFS, 66.4% vs 52.6%, P = 0.008). However, there was no difference overall in PFS or OS in either the full or propensity-matched cohort. Treatment with ICI and chemotherapy concurrently vs sequentially was associated with similar PFS (log-rank P = 0.12). Conclusions: In this real-world cohort, the addition of chemotherapy to ICIs may protect against early progression but does not influence long-term outcomes. Treatment with sequential vs concurrent ICI and chemotherapy produced similar outcomes. These findings suggest that combination therapy may maximally benefit patients at risk of early progression.
Naxitamab (NAX) treatment for refractory/relapsed (R/R) high-risk neuroblastoma (HR-NB): Response data and efficacy in patient (pt) subgroups.
Authors: Jaume Mora, Godfrey Chi-Fung Chan, Daniel A. Morgenstern, Karsten Nysom, Melissa Bear, Karen Tornøe, Per Settergren Sørensen, Brian H. Kushner
Journal: Journal of Clinical Oncology (2022)

e22019 Background: Almost half of pts with NB present with high-risk disease, most of whom experience persistence of disease or disease progression. Further, residual disease in the bone/bone marrow (BM) can drive relapse. NAX is a humanized GD2-binding monoclonal antibody indicated under accelerated approval in the US with GM-CSF for the treatment of R/R HR-NB in the bone/BM in pts ≥1 year of age with a partial response (PR), minor response (MR), or stable disease (SD) to prior therapy. Here we characterize the response data of NAX overall and efficacy in pt subgroups. Methods: Trial 201 is an ongoing registrational phase II trial evaluating NAX in pts with R/R HR-NB. Pts with progressive or residual soft tissue disease were excluded. NAX was administered over 30-60 min in the outpatient setting on Days 1/3/5 at 3 mg/kg/day with GM-CSF at 250 µg/m 2 /day on Days –4 to 0 and 500 µg/m 2 /day on Days 1 to 5; cycles were every 4 wks. Efficacy was evaluated by independent pathology and radiology review per revised International Neuroblastoma Response Criteria. Results: Results presented here are from an ad hoc interim analysis (Aug 5, 2020) of 48 pts (safety population) and 36 (efficacy population). Pts in the efficacy population received a median of 7 cycles (range 1–11). Overall response rate (ORR; complete response [CR] + PR) was 58% (44% CR; Table). Of the 9 responders who had PR initially, 4 improved to CR. Median number of cycles before onset of response (CR or PR) was 2 (range 2–8) and median time to onset of response (CR or PR) was 7.3 wks (95% CI 6–17). Median duration of response was 24.9 wks (95% CI 25–not estimable). The most common adverse events (CTCAE graded) were infusion-related reactions including hypotension and pain, which occurred in 98% and 96% of pts, respectively. Adverse events were managed with established guidelines. Conclusions: NAX provided a clinically meaningful response in pts with R/R HR-NB limited to bone/BM – frequent sites of residual disease. Response rates were generally consistent across subgroups. These efficacy results combined with a manageable safety profile and use in the outpatient setting demonstrate that NAX addresses a significant unmet medical need. Clinical trial information: NCT03363373. [Table: see text]